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The epsin N-terminal homology (ENTH) domain is a structural domain that is found in proteins involved in endocytosis and cytoskeletal machinery. Structure This domain is approximately 150 amino acids in length and is always found located at the N-termini of proteins. The domain forms a compact globular structure, composed of nine alpha-helices connected by loops of varying length. The general topology is determined by three helical hairpins that are stacked consecutively with a right hand twist. An N-terminal helix folds back, forming a deep basic groove that forms the binding pocket for the Ins(1,4,5)P3 ligand. The lipid ligand is coordinated by residues from surrounding alpha-helices and all three phosphates are multiply coordinated. Interactions with the lipid bilayer Proteins containing this domain have been found to bind PtdIns(4,5)P2 and Ins(1,4,5)P3 suggesting that the domain is a membrane-interacting module. The main function of proteins containing this domain appear ...
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Structural Domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer after ...
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Endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Pathways Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is .... *Clathrin-mediated endocytosis is mediated by the production of smal ...
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Cytoskeletal
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements. A multitude of functions can be performed by the cytoskeleton. Its primary function is to give the cell its shape and mechanical resistance to deformation, and through association with extracellular connective tissue and other cells it stabilizes entire tissues. The cytoskeleton can also contract, thereby deforming the cell and the cell's environment and allowing cells to migrate. Moreover, it is involved in many cell signaling pathways and in the uptake of extracellular material ( endocytosis), the ...
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PtdIns(4,5)P2
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. Signaling pathways PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. Recently, it has been found in the nucleus with unknown function. Functions Cytoskeleton dynamics near membranes PIP2 regulates the organization, polymerization, and branc ...
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Inositol Triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals. Properties Chemical formula and molecular weight IP3 is an organic molecule with a molecular mass of 420.10 g/mol. Its empirical formula is C6H15O15P3. It is composed of an inositol ring with three phosphate groups bound at the 1, 4, and 5 carbon positions, and three h ...
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Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle, hence the protein's name, which is derived from the Latin ''clathrum'' meaning lattice. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection. Structure The clathrin triskelion is composed of three clathrin heavy chains inter ...
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Epsin
Epsins are a family of highly conserved membrane proteins that are important in creating membrane curvature. Epsins contribute to membrane deformations like endocytosis, and block Vesicle (biology), vesicle formation during mitosis. Structure Epsin contains various protein domains that aid in function. Starting at the N-terminus is the ENTH domain. ENTH stands for Epsin N-Terminal Homolog. The ENTH domain is approximately 150 amino acids long and is highly conserved across species. It is composed of seven Alpha helix, α-helices and an eighth helix that is not aligned with the seven helices that make up a superhelical fold. The role of the ENTH domain is to bind membrane lipids which is currently thought to aid in the invagination of the plasma membrane to form clathrin-coated vesicles. Additionally, located toward the C-terminus of the ENTH domain are two to three ubiquitin interacting motifs which aids in ubiquitin dependent recruitment. Following the ENTH domain there is not ...
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Liposome
A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes (such as by sonication). Liposomes are most often composed of phospholipids, especially phosphatidylcholine and cholesterol, but may also include other lipids, such as egg, phosphatidylethanolamine, as long as they are compatible with lipid bilayer structure. A liposome design may employ surface ligands for attaching to unhealthy tissue. The major types of liposomes are the multilamellar vesicle (MLV, with several lamellar phase lipid bilayers), the small unilamellar liposome vesicle (SUV, with one lipid bilayer), the large unilamellar vesicle ( ...
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CLINT1
Clathrin interactor 1 (CLINT1), also known as EPSIN4, is a protein which in humans is encoded by the ''CLINT1'' gene. Function The CLINT1 protein binds to the terminal domain of the clathrin heavy chain and stimulates clathrin cage vesicle assembly. Clathrin coated vesicles enable neurotransmitter receptors and other proteins to be endocytosed or taken up across neuronal membranes and across the membranes of other types of cells. This enables a turnover of neuroreceptors or other proteins to be maintained and thus the numbers of receptors can be fine tuned. Clinical significance The ''CLINT1'' gene has been shown to be involved in the genetic aetiology of schizophrenia in four studies It is known that the antipsychotic drugs chlorpromazine and clozapine stabilise clathrin coated vesicles and this may be one reason why antipsychotic drugs are effective in treating delusions, auditory hallucinations and many of the other symptoms of schizophrenia. Interactions CLINT1 has be ...
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ENTHD1
ENTH domain-containing protein 1, also known as Epsin-2B and ENTHD1, is a protein that in humans is encoded by the ''ENTHD1'' gene.UniProt ID: Retrieved 19 January 2020 Gene The ''ENTHD1'' gene is located on human chromosome 22. Expression ENTHD1 proteins are expressed in 26 human organs, with the highest expression in the testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster .... References

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EPN2
Epsin-2 is a protein that in humans is encoded by the ''EPN2'' gene. This gene encodes a protein which interacts with clathrin and adaptor-related protein complex 2, alpha 1 subunit. The protein is found in a brain-derived clathrin-coated vesicle fraction and localizes to the peri-Golgi region and the cell periphery. The protein is thought to be involved in clathrin-mediated endocytosis. Alternate splicing of this gene results in two transcript variants encoding different isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof .... References Further reading

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